Tissues of the eye depend on families of specialized proteins. In the lens, the major proteins the crystallins. We have shown that in humans and other species, crystallins have arisen by a process called Gene Recruitement. Proteins such as enzymes and stress proteins have been recruited to serve an additionl structural role in lens transparency. The origins and functions of many classes of crystallins have been elucidated. Currently we are investigating the last major group for which a function is unknown. These are the related beta(b) and gamma (g) crystallins. Non-lens relatives of these proteins with stress and cancer related functions have been identified. This includes a novel gene expressed in retinal pigment epithelium. This "new gamma" (ng) has a gene structure that combines features of both b and g gene families. Ng has been cloned from human and mouse. At the same time, an apparent homolog has also been cloned in studies of the complement of crystallins in a reptile, the iguana, suggesting that this gene is well-conserved in evolution. We have shown that gS-crystallin is the major bg-crystallin in the adult human lens. In mouse, the gS gene is the locus of the Opj cataract. The Opj mice provide evidence for a role of gS in control of lens fiber cell structure. Recombinant wild type and mutant proteins for gS have been produced for functional studies. The mutant protein in Opj contains a temperature-sensitive destablizing mutation. Around mouse body temperature one domain unfolds and causes the protein to become insoluble. Recombinant protein is being used in both x-ray crystallographic and NMR structure studies. To separate the issues of mal-folded protein and loss-of-function in the Opj cataract, homologous recombination, "knock-out" mice for the gS gene have been created. In some species enzymes have been recruited as crystallins. We have produced recombinant protein for one of these, eta-crystallin, which is a retinaldehyde dehydrogenase that acts as a major crystallin in elepant shrews (macroscelids). A crystal structure has been determined in collaboration with the Birkbeck College group. This structure shows that the NAD(H) cofactor is avidly bound in the crystallized protein. This is consistent with the idea that eta-crystallin may have a protective role in the lens, sequestering NADH has a UV filter to reduce glare and protect against damage from bright sunlight.